Evidence has accumulated that digitalis-like factor (EDLF) may play an important role in the pathogenesis of cardiovascular disease (hypertension, congestive heart failure, acute myocardial infarction) via their ability to inhibit sodium pump activity. Much attention has been paid to one of these factors, an endogenous ouabain; however, a digoxin- like immunoreactive factor has also been found previously to contribute to arrythmogenesis in myocardial ischemia. The objectives of this project are to clarify the role of various sodium pump inhibitors, especially the digoxin-like immunoreactive EDLF, in blood pressure regulation. During the past year, studies were completed with anesthetized dogs which showed that the increases in endogenous digitalis-like factors, which are evoked by rapid expansion of plasma volume, include a bufodienolide compound in higher concentrations than a concurrently observed digoxin- like factor. Pretreatment of the animals with an antidigitalis antibody prevented the rapidly developing increases in cardiac contractility and more slowly developing natriuresis. A second study showed that voluntary hypoventilatory breathing in human subjects maintained by feedback from a respiratory gas monitor was also associated with increased in urinary excretion of the bufodienolide compound which persisted for 30 minutes following cessation of the breathing task. These studies have implications for understanding of the origins of hypertension and for development of new pharmacological interventions in cardiovascular disorders.